Role of dendritic cell subsets in glomerulonephritis

树突状细胞亚群在肾小球肾炎中的作用

• 批准号: 138669427
• 负责人: Professor Dr. Christian Kurts
• 金额: --
• 依托单位: Institut für Experimentelle Immunologie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/138669427?language=en
• 关键词: Role; dendritic; cell; subsets; glomerulonephritis

We recently reported that activation of kidney dendritic cells (kDCs) drives progression of nephrotoxic glomerulonephritis (NTN), a model of human crescentic GN (cGN), by mechanisms involving chemokine-mediated recruitment of immune effector cells. By contrast, immature kDCs attenuated cGN by chemokine-mediated recruitment of immunosuppressive natural killer T cells (NKT cells) and regulatory T cells (Tregs,) whose function surprisingly depended on the transcription factor NF-κB. Furthermore, we found that Batf3-dependent kDCs, a small subset of DCs characterized in the kidney by CD103 expression, possess a surprisingly strong protective functionality in NTN. In the next funding period, we wish to clarify the mechanisms underlying the function of Batf3-dependent and -independent kDCs. We will 1. Study the role of Batf3-dependent kDCs on the systemic Th1 cell immune response against the kidney; 2. Distinguish between effects of Batf3-dependent and -independent kDCs in NTN, with a particular focus on potential interactions with suppressive iNKT cells and Tregs; 3. Clarify how kidney DC function turns pro-inflammatory in chronic NTN, by distinguishing whether the ratio between protective and pro-inflammatory DCs shifts towards the latter or whether protective DCs mature and lose their protective functionality, for example through NF-κB; and 4. Clarify which kDC subsets migrate to the renal lymph node in NTN. We expect that knowledge of the roles of DCs and their regulatory functions in cGN may facilitate developing new DC-targeted therapies for GN.

我们最近报道，肾树突状细胞（kDCs）的激活驱动进展的肾毒性肾小球肾炎（NTN），人新月体GN（cGN）的模型，涉及趋化因子介导的免疫效应细胞的招聘机制。相比之下，未成熟的kDC通过趋化因子介导的免疫抑制性自然杀伤T细胞（NKT细胞）和调节性T细胞（TKT细胞）的募集来减弱cGN，其功能出人意料地依赖于转录因子NF-κB。此外，我们发现Batf 3依赖性kDCs，一小部分DCs在肾脏中通过CD 103表达来表征，在NTN中具有令人惊讶的强保护功能。在下一个资助期，我们希望阐明Batf 3依赖性和非依赖性kDC的功能机制。我们将1。研究Batf 3依赖性kDCs在系统性Th 1细胞抗肾脏免疫应答中的作用。区分Batf 3依赖性和非依赖性kDC在NTN中的作用，特别关注与抑制性iNKT细胞和TdR的潜在相互作用; 3.通过区分保护性和促炎性DC之间的比例是否向后者转移或保护性DC是否成熟并失去其保护功能，例如通过NF-κB，阐明肾脏DC功能如何在慢性NTN中变成促炎性;和4.阐明NTN中哪些kDC亚群迁移至肾淋巴结。我们希望了解DC的作用及其在cGN中的调节功能，可能有助于开发新的DC靶向治疗GN的方法。